Macrophage Uncoupling Protein-2 Regulation And Expression In Inflammatory Joint Disease And Hyperoxic Lung Damage
Funder
National Health and Medical Research Council
Funding Amount
$270,013.00
Summary
Oxygen radicals (OR) are made by white blood cells (WBC) when they protect against microbes and cancer cells. However, excessive production also damages normal tissue, for example in lungs that receive too much oxygen (hyperoxic lung damage) or in inflamed joints. One type of WBC, the macrophage has a protein named UCP2, that limit the amount of OR formation. This project aims to find out how macrophages activate UCP2 and whether they do so in inflammatory arthritis and hyperoxic lung damage.
Regulation Of Skeletal Muscle AMP-activated Protein Kinase By Glycogen
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
The enzyme AMP protein kinase has three parts (subunits) and is central to controlling the body's metabolism. We have discovered that one subunit is essential for tightly associating the enzyme with muscle glycogen which is a source of high energy and efficient metabolism. We will identify where the enzyme attaches to glycogen, and how diet and exercise alter this association. Understanding this could lead to new approaches for treating Type 2 diabetes where energy metabolism is disrupted.
The Structural Basis Of Ligand-Induced Activation Of The Insulin Receptor
Funder
National Health and Medical Research Council
Funding Amount
$640,825.00
Summary
We aim to understand how insulin binds to and activates its cell-surface receptor. This information has implications for the design of anti-diabetic agents targetted directly to the insulin receptor. Diabetes is a global health problem and is classified by the World Health Organization as an epidemic. The results also have implications for the insulin-like growth factor receptor system and the design of anti-cancer therapeutics directed towards it .
How The Bcl-2 Protein Family Controls Apoptosis And Impacts On Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
Impaired cell death (apoptosis) is now recognized as an important step towards cancer and a major barrier to effective therapy. The discoveries on apoptosis by Professor Jerry Adams and colleagues have galvanized the search for drugs that engage the cell’s apoptotic machinery as a new way to treat cancer. His proposed studies aim to clarify how apoptosis is controlled and how the control goes awry in cancer, and to determine how such drugs can be most effectively used to improve cancer treatment ....Impaired cell death (apoptosis) is now recognized as an important step towards cancer and a major barrier to effective therapy. The discoveries on apoptosis by Professor Jerry Adams and colleagues have galvanized the search for drugs that engage the cell’s apoptotic machinery as a new way to treat cancer. His proposed studies aim to clarify how apoptosis is controlled and how the control goes awry in cancer, and to determine how such drugs can be most effectively used to improve cancer treatment.Read moreRead less
I am a biochemist determining how metabolism is controlled in response to energy supply and demand. This is important in order to understanding how diet and exercise are beneficial to health.
Activation Of HSP70: A Therapeutic Target To Treat Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$467,720.00
Summary
Type 2 diabetes is a prevalent and serious disease and the development of new strategies to treat it is warranted. In recent experiments we have been able to show that by upregulating a particular protein, referred to as a heat shock protein, we can reduce the clinical markers of type 2 diabetes by reducing key inflammatory pathways known to lead to insulin resistance. In this series of studies we will investigate whether activation of this protein is a target for therapeutic treatment.
Structural Basis For Restraint And Activation Of Pro-apoptotic Bax And Bak
Funder
National Health and Medical Research Council
Funding Amount
$246,478.00
Summary
The aim of this project is to understand how cell death is controlled. Defects in the cell death machinery occur in many cancers, making that machinery an attractive target for cancer therapeutics. My experiments will yield atomic resolution pictures of the functional machinery, illustrating for the first time how the molecular brakes are applied to prevent cells dying. Understanding these structures will aid the discovery of drugs that can activate the cell death machinery in cancer cells.